1. Field of the Invention
This invention relates to the field of tissue engineering, and more particularly to a system and method for producing a cardiac muscle construct in vitro.
2. Background Art
At present, three-dimensional tissues are capable of being produced in vitro using various types of cells. For example, U.S. Pat. No. 5,443,950 issued to Naughton et al. describes three-dimensional cultures for bone marrow, skin, liver, vascular, and pancreatic tissues which are grown within synthetic matrices. In these tissues as well as others, investigators have been successful in proliferating cells and tissues in vitro such that the resulting three-dimensional tissues, termed “organoids” or “constructs”, display many of the characteristics of their in vivo counterparts. These constructs have a variety of foreseeable applications, ranging from transplantation in vivo to functional and pharmacological testing in vitro.
In terms of muscle tissue, in vitro constructs of smooth muscle, skeletal muscle, and cardiac muscle have each been formulated. For cardiac muscle, U.S. Pat. No. 4,605,623 issued to Malette et al., for example, describes a method for cultivating the three-dimensional growth of cardiac myocytes within a chitosan scaffold material. Although this and other scaffold-based cardiac tissue constructs have been reported (see Atkins et al., Tissue Eng 5, 103-18, April 1999; Akhyari et al., Circulation 106, I137-42, September 2002; Bursac et al., Am J Physiol 277, H433-44, August 1999; Carrier et al., Biotechnol Bioeng 64, 580-9, September 1999; Fink et al., Faseb J 14, 669-79, April 2000; Kofidis et al., J Thorac Cardiovasc Surg 124, 63-9, July 2002; Kofidis et al., Eur J Cardiothorac Surg 22, 238-43, August 2002; Leor et al., Circulation 102, I1156-61, November 2000; Zimmerman et al., Circ Res 90, 223-30, February 2002; Zimmerman et al., Circulation 106, I151-7, September 2002; Taylor et al., J Heart Valve Dis 11, 298-307, May 2002; Papadaki et al., Am J Physiol Heart Circ Physiol 280, H168-78, January 2001; McDevitt et al., J Biomed Mater Res 60, 472-9, June 2002), the creation of a self-organizing contractile cardiac muscle construct in culture has proven elusive. There are many reasons for this, including the fact that cardiac myocytes are post-mitotic such that they no longer undergo cell division to produce greater numbers of cells, making it difficult or impossible to amplify cardiac myocytes in culture.